Title (fr)

Publication

Application

Priority

US 9822557 W 19981023

US 95665797 A 19971023

Abstract (en)

[origin: WO9920791A1] Methods for treating and preventing the onset and maintainance of multiple drug resistance (MDR) in animals undergoing chemotherapy for cancer are provided wherein target cells are depleted of adenosine 5'-monophosphate (AMP) and adenosine 5'-triphosphate (ATP) such that the cells are unable to support P-glycoprotein activity. One method obtains a population of target cells from a host and assays for loss of methylthioadenosine phosphorylase (MTAse) activity. MTAse catabolizes methylthioadenosine to adenine for endogenous salvage incorporation into the intracellular AMP pool. MTAse deficient cells are treated with a purine synthesis inhibitor, such as L-alanosine, which starves the cells of adenine and suppress P-glycoprotein activity. MTAse competent cells are also treated for MDR with purine synthesis inhibitors. MTAse competent and deficient cells are also treated for maligancy with other anti-cancer drugs. The figure depicts the effect of chemotherapeutic drugs on the cell lines.